Methods for producing folic acid have been described. Robert B. Angler et al. (JACS, 70 (1948), 25) describe the manufacture of folic acid using halogen-free compounds by reacting p-aminobenzoyl-L-glutamic acid diethyl ester with 2-hydroxymalondialdehyde, isolating p-(2,3-dihydroxy-2-ene-propylideneamino)-benzoic acid diethyl ester and reacting the intermediate with triaminopyrimidinone. In this synthesis, in which an imine is isolated as the intermediate, folic acid is obtained in only 12.6% yield.
Other methods for producing folic acid are described in O. Isler, G Brubacher, S. Ghisla, B. Krautler, Vitamine II; G. Thieme Verlag Stuttgart; (1988).
These methods for producing folic acid described to date have the common disadvantage of resulting in a low yield of folic acid.
The object of the present invention is to provide a process for the production of folic acid in substantially higher yield (up to 84%) compared with known processes, by using a novel diimine as an intermediate.
The production of diimines has been described. B. Eistert et al. (Chem. Ber., 88 (1955), 939) describe the production of diimines by reacting 2-hydroxy malondialdehyde with aromatic amines such as aniline, p-aminobenzoic acid or p-amino benzoic acid ester.